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Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 PLoS+One 2015 ; 10 (4): ä Nephropedia Template TP
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Intravenous Infusion of Monocytes Isolated from 2-Week-Old Mice Enhances Clearance of Beta-Amyloid Plaques in an Alzheimer Mouse Model #MMPMID25830951
Hohsfield LA; Humpel C
PLoS One 2015[]; 10 (4): ä PMID25830951show ga
Alzheimer?s disease (AD) is characterized by the deposition of ?-amyloid (A?) senile plaques and tau-associated neurofibrillary tangles. Other disease features include neuroinflammation and cholinergic neurodegeneration, indicating their possible importance in disease propagation. Recent studies have shown that monocytic cells can migrate into the AD brain toward A? plaques and reduce plaque burden. The purpose of this study was to evaluate whether the administration of intravenous infusions of ?young? CD11b-positive (+) monocytes into an AD mouse model can enhance A? plaque clearance and attenuate cognitive deficits. Peripheral monocytes were isolated from two-week-old wildtype mice using the Pluriselect CD11b+ isolation method and characterized by FACS analysis for surface marker expression and effective phagocytosis of 1 ?m fluorescent microspheres, FITC-Dextran or FITC-A?1?42. The isolated monocytes were infused via the tail vein into a transgenic AD mouse model, which expresses the Swedish, Dutch/Iowa APP mutations (APPSwDI). The infusions began when animals reached 5 months of age, when little plaque deposition is apparent and were repeated again at 6 and 7 months of age. At 8 months of age, brains were analyzed for A?+ plaques, inflammatory processes and microglial (Iba1) activation. Our data show that infusions of two-week-old CD11b+ monocytes into adult APPSwDI mice results in a transient improvement of memory function, a reduction (30%) in A? plaque load and significantly in small (<20 ?m) and large (>40 ?m) plaques. In addition, we observe a reduction in Iba1+ cells, as well as no marked elevations in cytokine levels or other indicators of inflammation. Taken together, our findings indicate that young CD11b+ monocytes may serve as therapeutic candidates for improved A? clearance in AD.